Ribonucleases with Antiproliferative Properties: Molecular Biological and Biochemical Characteristics

VS Pokrovskii1, EM Treshchalina1, NV Andronova1, SM Deev2

1 N.N. Blokhin Russian Cancer Research Center, 24 Kashirskoye sh., Moscow, Russian Federation, 115478

2 M.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, 16/10 Miklukho-Maklaya str., Moscow, Russian Federation, 117997

For correspondence: Vadim Sergeevich Pokrovskii, PhD, 24 Kashirskoye sh., Moscow, Russian Federation, 115478; Tel.: +7(499)324-14-09; e-mail: vadimpokrovsky@yandex.ru

For citation: Pokrovskii VS, Treshchalina EM, Andronova NV, Deev SM. Ribonucleases with Antiproliferative Properties: Molecular Biological and Biochemical Characteristics. Clinical oncohematology. 2016;9(2):130–7 (In Russ).

DOI: 10.21320/2500-2139-2016-9-2-130-137


ABSTRACT

The article dwells on ribonucleases (RNAses) whose cytotoxic activity depends on the enzymatic activity, i.e. the ability to catalyze the cleavage of phosphodiester bonds of RNA. It presents both well-known information and our own data on RNAses of different origins with antitumor properties; it investigates the relation between the mechanism of cytotoxicity and biochemical and molecular biological characteristics. The analysis of published data demonstrates that all above characteristics contribute to the antiproliferative activity of RNAses. The major challenge for this group of enzymes is the achieving of selective bioavailability. This problem can be solved by creating conjugates as in case with ranpirnase and barnase. Based on their major pharmacological properties, active antitumor RNAses have great perspectives for treatment of not only oncohematological, but also solid malignancies.


Keywords: ribonucleases, ranpirnase, amphinase, binase, barnase, pharmacological properties.

Received: January 4, 2016

Accepted: January 7, 2016

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Enzymes in oncohematology: relevant directions of experimental studies and prospects of clinical use

V.S. Pokrovskiy and H.M. Treshchalina

N.N. Blokhin Russian Cancer Research Center of RAMS, Moscow, Russian Federation


ABSTRACT

Recently, the field of development of the novel enzyme-based drugs showed remarkable advances. In addition to L-asparaginase which have been already used in oncohematology for more than 30 years, the two new enzymes, L-arginine deiminase and ranpirnase, underwent the several phases of clinical trials. Anticancer activity in vivo at the preclinical stage was shown for a number of enzymes: L-methionine-gamma-lyase, L-lysine-alpha-oxydase, and binase. This review discusses the enzymes which possess anticancer activity and prospects for their use in oncohematology.


Keywords: anticancer enzymes, L-asparaginase, L-methionine gamma-lyase, L-lysine alpha-oxydase, L-arginine deiminase, L-phenylalanine ammonia-lyase, ranpirnase.

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